Planck 2013 results. XI. All-sky model of thermal dust emission

Peer reviewe

Planck 2013 results. XXII. Constraints on inflation

We analyse the implications of the Planck data for cosmic inflation. The Planck nominal mission temperature anisotropy measurements, combined with the WMAP large-angle polarization, constrain the scalar spectral index to be n(s) = 0.9603 +/- 0:0073, ruling out exact scale invariance at over 5 sigma Planck establishes an upper bound on the tensor-to-scalar ratio of r = 2 do not provide a good fit to the data. Planck does not find statistically significant running of the scalar spectral index, obtaining dn(s)/dln k = -0.0134 +/- 0.0090. We verify these conclusions through a numerical analysis, which makes no slowroll approximation, and carry out a Bayesian parameter estimation and model-selection analysis for a number of inflationary models including monomial, natural, and hilltop potentials. For each model, we present the Planck constraints on the parameters of the potential and explore several possibilities for the post-inflationary entropy generation epoch, thus obtaining nontrivial data-driven constraints. We also present a direct reconstruction of the observable range of the inflaton potential. Unless a quartic term is allowed in the potential, we find results consistent with second-order slow-roll predictions. We also investigate whether the primordial power spectrum contains any features. We find that models with a parameterized oscillatory feature improve the fit by delta 2 10; however, Bayesian evidence does not prefer these models. We constrain several single-field inflation models with generalized Lagrangians by combining power spectrum data with Planck bounds on fNL. Planck constrains with unprecedented accuracy the amplitude and possible correlation (with the adiabatic mode) of non-decaying isocurvature fluctuations. The fractional primordial contributions of cold dark matter (CDM) isocurvature modes of the types expected in the curvaton and axion scenarios have upper bounds of 0.25% and 3.9% (95% CL), respectively. In models with arbitrarily correlated CDM or neutrino isocurvature modes, an anticorrelated isocurvature component can improve the 2 by approximately 4 as a result of slightly lowering the theoretical prediction for the 40 multipoles relative to the higher multipoles. Nonetheless, the data are consistent with adiabatic initial conditions.Peer reviewe

Long-term follow up of families with pathogenic NFKB1 variants reveals incomplete penetrance and frequent inflammatory sequelae

Publisher Copyright: © 2022 The AuthorsNuclear factor κ light-chain enhancer of activated B cells (NF-κB) family of evolutionarily conserved transcription factors are involved in key cellular signaling pathways. Previously, hypogammaglobulinemia and common variable immunodeficiency (CVID)-like phenotypes have been associated with NFKB1 variants and loss-of-function NFKB1 variants have been reported as the most common monogenic cause for CVID among Europeans. Here, we describe a Finnish cohort of NFKB1 carriers consisting of 31 living subjects in six different families carrying five distinct heterozygous variants. In contrast to previous reports, the clinical penetrance was not complete even with advancing age and the prevalence of CVID/hypogammaglobulinemia was significantly lower, whereas (auto)inflammatory manifestations were more common (42% of the total cohort). At current stage of knowledge, routine genetic screening of asymptomatic individuals is not recommended, but counseling of potential adult carriers seems necessary.Peer reviewe

Characterization of Expanded Gamma Delta T Cells from Atypical X-SCID Patient Reveals Preserved Function and IL2RG-Mediated Signaling

Abnormally high gamma delta T cell numbers among individuals with atypical SCID have been reported but detailed immunopheno typing and functional characterization of these expanded gamma delta T cells are limited. We have previously reported atypical SCID phenotype caused by hypomorphic IL2RG (NM_000206.3) c.172C > T;p.(Pro58Ser) variant. Here, we have further investigated the index patient's abnormally large gamma delta T cell population in terms of function and phenotype by studying IL2RG cell surface expression, STAT tyrosine phosphorylation and blast formation in response to interleukin stimulation, immunophenotyping, TCRv gamma sequencing, and target cell killing. In contrast to his alpha beta T cells, the patient's gamma delta T cells showed normal IL2RG cell surface expression and normal or enhanced IL2RG-mediated signaling. V delta 2 + population was proportionally increased with a preponderance of memory phenotypes and high overall tendency towards perforin expression. The patient's gamma delta T cells showed enhanced cytotoxicity towards A549 cancer cells. His TCRv gamma repertoire was versatile but sequencing of IL2RG revealed a novel c.534C > A; p.(Phe178Leu) somatic missense variant restricted to gamma delta T cells. Over time this variant became predominant in gamma delta T cells, though initially present only in part of them. IL2RG-Pro58Ser/Phe178Leu variant showed higher cell surface expression compared to IL2RG-Pro58Ser variant in stable HEK293 cell lines, suggesting that somatic p.(Phe178Leu) variant may at least partially rescue the pathogenic effect of germline p.(Pro58Ser) variant. In conclusion, our report indicates that expansion of gamma delta T cells associated with atypical SCID needs further studying and cannot exclusively be deemed as a homeostatic response to low numbers of conventional T cells.Peer reviewe

Novel Hemizygous IL2RG p.(Pro58Ser) Mutation Impairs IL-2 Receptor Complex Expression on Lymphocytes Causing X-Linked Combined Immunodeficiency

Hypomorphic IL2RG mutations may lead to milder phenotypes than X-SCID, named variably as atypical X-SCID or X-CID. We report an 11-year-old boy with a novel c. 172C>T;p.(Pro58Ser) mutation in IL2RG, presenting with atypical X-SCID phenotype. We also review the growing number of hypomorphic IL2RG mutations causing atypical X-SCID. We studied the patient's clinical phenotype, B, T, NK, and dendritic cell phenotypes, IL2RG and CD25 cell surface expression, and IL-2 target gene expression, STAT tyrosine phosphorylation, PBMC proliferation, and blast formation in response to IL-2 stimulation, as well as protein-protein interactions of the mutated IL2RG by BioID proximity labeling. The patient suffered from recurrent upper and lower respiratory tract infections, bronchiectasis, and reactive arthritis. His total lymphocyte counts have remained normal despite skewed T and B cells subpopulations, with very low numbers of plasmacytoid dendritic cells. Surface expression of IL2RG was reduced on his lymphocytes. This led to impaired STAT tyrosine phosphorylation in response to IL-2 and IL-21, reduced expression of IL-2 target genes in patient CD4+ T cells, and reduced cell proliferation in response to IL-2 stimulation. BioID proximity labeling showed aberrant interactions between mutated IL2RG and ER/Golgi proteins causing mislocalization of the mutated IL2RG to the ER/Golgi interface. In conclusion, IL2RG p.(Pro58Ser) causes X-CID. Failure of IL2RG plasma membrane targeting may lead to atypical X-SCID. We further identified another carrier of this mutation from newborn SCID screening, lost to closer scrutiny.Peer reviewe

Bioleaching and recovery of metals from final slag waste of the copper smelting industry

Solid waste from the copper smelting industry may be harmful if disposed of in the environment, but it may be a valuable resource if metals can be recovered. The purpose of this study was to evaluate the acid bioleaching of metals from a sample of final smelter slag and the recovery of metals from the leach liquors. Bioleaching was tested in a continuously stirred tank reactor (CSTR) at 20-25 degrees C with 5% pulp density (particle size 75% <47 mu m). The yields of metal solubilization after 29 days of contact were 41% Fe, 62% Cu, 35% Zn and 44% Ni. Metals were precipitated in a separate CSTR by titrating the leach liquors with sulfide-rich effluent from a sulfate-reducing fluidized-bed reactor (FBR) (25 degrees C) to desired pH values. Over 98% of the Cu precipitated at pH >= 2.8 and over 99% of the Zn precipitated at pH >= 3.9. The precipitation of Ni and Fe required higher pH values and was less efficient than Cu and Zn recovery. In addition, bulk precipitation of metals was also tested by feeding the leach liquor directly to another sulfate-reducing FBR. In order to reduce its toxicity and maintain stable sulfate reduction performance in the FBR, the leach liquor had to be diluted ten-fold and the pH adjusted from 0.6 to approximately 4. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved

CD200 positive human mesenchymal stem cells suppress TNF-alpha secretion from CD200 receptor positive macrophage-like cells

Human mesenchymal stem cells (hMSCs) display immunosuppressive properties in vitro and the potential has also been transferred successfully to clinical trials for treatment of autoimmune diseases. OX-2 (CD200), a member of the immunoglobulin superfamily, is widely expressed in several tissues and has recently been found from hMSCs. The CD200 receptor (CD200R) occurs only in myeloid-lineage cells. The CD200-CD200R is involved in down-regulation of several immune cells, especially macrophages. The present study on 20 hMSC lines shows that the CD200 expression pattern varied from high (CD200Hi) to medium (CD200Me) and low (CD200Lo) in bone marrow-derived mesenchymal stem cell (BMMSC) lines, whereas umbilical cord blood derived mesenchymal stem cells (UCBMSCs) were constantly negative for CD200. The role of the CD200-CD200R axis in BMMSCs mediated immunosuppression was studied using THP-1 human macrophages. Interestingly, hMSCs showed greater inhibition of TNF-α secretion in co-cultures with IFN-γ primed THP-1 macrophages when compared to LPS activated cells. The ability of CD200Hi BMMSCs to suppress TNF-α secretion from IFN-γ stimulated THP-1 macrophages was significantly greater when compared to CD200Lo whereas UCBMSCs did not significantly reduce TNF-α secretion. The interference of CD200 binding to the CD200R by anti-CD200 antibody weakened the capability of BMMSCs to inhibit TNF-α secretion from IFN-γ activated THP-1 macrophages. This study clearly demonstrated that the efficiency of BMMSCs to suppress TNF-α secretion of THP-1 macrophages was dependent on the type of stimulus. Moreover, the CD200-CD200r axis could have a previously unidentified role in the BMMSC mediated immunosuppression.Peer reviewe

Oxide scale formation of EN 1.4622 and EN 1.4828 stainless steels during annealing and descaling behavior in neutral electrolytic pickling

Abstract Oxide scale formation during short-term annealing and electrolytic pickling behavior of ferritic EN 1.4622 and austenitic EN 1.4828 stainless steels are investigated. The annealing is performed at temperatures between 1000 and 1100 °C for ferritic and 1100 and 1200 °C for austenitic steel grade under humid atmospheres in simulated industrial process. Neutral electrolytic pickling, also referred to as neutral electrochemical pickling or the Ruthner Neolyte Process, is performed in Na₂SO₄ electrolyte, and pickling efficiency is evaluated visually and by image analysis of pickled surfaces. The results show that annealing conditions have a more impactful effect on the structure and the composition of the resulting oxide in the austenitic grade within the studied condition range. The thicknesses of the ferritic scales are mainly less than 0.4 μm, while almost all austenitic scales are thicker than it. In addition, the amount of silicon oxide formation inside the steel matrix of the austenitic and ferritic grades is highly different. Longer exposure times and higher temperatures promote scale growth during annealing, resulting in inefficient electrolytic pickling for the ferritic grade. For the austenitic grade, almost all steel surfaces are still covered with oxide scale after electrolytic pickling

Effect of simulated annealing conditions on scale formation and neutral electrolytic pickling

Abstract Scale formation of AISI 304 stainless steel during annealing at temperatures between 1100 and 1200 °C under a water vapor‐containing atmosphere is studied. Characterization of the oxide scale is performed with field‐emission scanning electron microscopy–energy dispersive spectroscopy (FESEM–EDS) and glow discharge optical emission spectroscopy (GDOES) and removal of oxide scale is done via neutral electrolyte pickling. The pickling conditions are kept constant and the effect of the annealing conditions and scale properties on the pickling result are examined. The effectiveness of pickling is evaluated using analysis FESEM images taken on polished sections of pickled surfaces. Research shows that the thickness, morphology, and composition of the oxide scale are dependent on annealing temperature and time. The thicknesses of the scale formed under the established conditions vary from 0.2 to over 30 μm, and morphologies between the chromium rich oxide layer and layered scale structure formed by breakaway oxidation. The pickling response of oxide scales remains good at all annealing temperatures with the shortest exposure time